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Description of key information

There are two acute oral, and one acute dermal toxicity studies that demonstrate lack of toxicity of dilauroyl peroxide at the limit dose (2000 mg/kg,  5000 mg/kg and 2000 mg/kg, respectively).  In addition an inhalation study with limited documentation, also demonstrates lack of toxicity at concentrations (200 mg/l dust) well above the limit concentration, as well as granulometry data which did not demonstrate significant inhalable particles.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Apparently well conducted GLP study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Young adult rats of the CD strain (remote Sprague-Dawley origin) were supplied by Charles River (U.K.) Limited, Margate, Kent, England. The animals
were bred under barriered conditions and traveled from the supplier to the animal holding room in sealed boxed with filter protected air-vents. The
albino rat was selected for this study as it has been widely accepted as the standard laboratory species for use in acute toxicity tests.
The strain has been used for toxicological purposes since its establishment under S.P.F. conditions in 1955.

The animals were housed in stainless steel grid cages (Stephen Clark Fabrications Limited, Alva, Clackmannanshire, Scotland). The grid floors
ensured rapid removal of waste material to undertrays which were cleaned out as necessary. Five animals of the same sex were accommodated in
each cage. The cages were suspended in mobile stainless steel racks.

The animals were held in a limited-access facility. All rooms were kept at slight positive pressure relative to the outside and each had its own filtered
air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature range of 18-21°C and a relative humidity
range of 38~57% R.H. were achieved. The small number of low humidity values (below 40%) did not have any overt effect on the well-being of the
animals. Electric time-switches regulated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the
electricity supply in the event of a power failure. All personnel entering the building changed into clean protective clothing and wore a gown, gloves,
plastic over-shoes and face mask to service animal-holding areas. A commercially-available complete pelleted rodent diet (RM-l S.Q.C., from Special Diets Services Limited, Witham, Essex, England) was fed without restriction, except for the removal of food for approximately 19 hours before
administration of the test material. The manufacturer supplied analytical data with each batch of diet which included concentrations of nutritional
components, aflatoxins and selected heavy metals, pesticides and micro-organisms. The diet contained no added antibiotic or other
chemotherapeutic or prophylactic treatment.

Animals had free access to tap water taken from the public supply; in England the supply and quality of this water is governed by Department of the
Environment regulations. Certificates of analysis were routinely received from the supplier (Suffolk Water Company). At approximately six-month
intervals water was routinely sampled for analysis, by a laboratory independent of the supplier, for selected chlorinated and organophosphorus
pesticides, polychlorinated biphenyls and lead and cadmium contaminants; it was also examined for coliform bacteria.
Results of these analyses are retained in the archives. There was no known information to indicate that normal levels of common contaminants, or
any specific contaminants, in the diet or drinking water would influence the outcome of the study.
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
The test material was prepared at the appropriate concentration in maize oil. The dosage was calculated and expressed gravimetrically in
terms of the material as received. A fresh formulation of the test material was prepared shortly before administration and any surplus remaining after dosing was destroyed on the same day.

Dose-volume was determined for each animal according to the fasted bodyweight on the morning of dosing. Dosing commenced on the morning of
Day 1.
Doses:
On the basis of of a preliminary study at 800 mg/kg bodyweight in which there were no mortalities, the main study was carried out using a single
group of five male and five female rats given a single oral administration of Laurox at the maximum practicable dosage of 2000 mg/kg (Regulatory
limit test), at a constant volume-dosage of 10 ml/kg in maize oil.

Dose-volume was determined for each animal according to the fasted bodyweight on the morning of dosing. Dosing commenced on the morning of Day 1. A flexible portex catheter (8-choke) was passed down the oesophagus allowing instillation of the dose into the lumen of the stomach. Each
animal was returned to its cage and food hoppers were refilled approximately three hours after dosing.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2
onwards, the animals were inspected twice daily (morning and afternoon). The type, time of onset and duration of reactions to treatment were
recorded. The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15. The test was terminated on the
morning of Day 15.

All animals were killed at termination of the study. Each animal was thoroughly examined for abnormality of tissues or organs. All body cavities were
opened, larger organs were sectioned and the gastro-intestinal tract was opened at intervals for examination of the mucosal surfaces. All
abnormalities were described or the normal appearance of major organs was confirmed. No tissues were retained in fixative.
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities.
Clinical signs:
Signs of reaction were confined to piloerection in all animals on the day of treatment. The animals were overtly normal on the following day.
Body weight:
The animals achieved expected bodyweight gains.
Gross pathology:
There were no significant macroscopic lesion.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of Laurox to rats was greater than 2000 mg/kg bodyweight.
Executive summary:

The study was conducted to determine the acute oral toxicity of Laurox to rats in accordance with OECD 401. Rats were administered the test article at 2000 mg/kg bodyweight via gavage and observed for 14 days.

There were no mortalities following the oral administration of Laurox at 2000 mg/kg bodyweight. Piloerection was noted in all animals on the day of dosing. There were no significant necropsy findings.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Apparently well conducted study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species, strain: rat, Sprague-Dawley Rj: SD (IOPS Han).
Reason for this choice: rodent species generally accepted by regulatory authorities for this type
of study.
Breeder: Janvier, Le Genest-Saint-Isle, France.
Age/weight: on the day of treatment, the animals were approximately 8 weeks old and had a
mean body weight ± standard deviation of 336 ± 21 g for the males and 220 ± 4 g for the females.
Acclimation: at least 5 days before the beginning of the study.
Identification: individually by earnotches.

The conditions in the animal room were set as follows:
• temperature: 22 ± 2°C
• relative humidity: 30 to 70%
• light/dark cycle: 12 h/12 h
• ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these
daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals.
During the acclimation period, one to seven animals of the same sex were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). During the treatment period, the animals were housed individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm).
Each cage contained autoclaved sawdust (SICSA, Alfortville, France). Sawdust is analyzed by the supplier for composition and contaminant levels.

All the animals had free access to adapted pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany). Each batch of food is analyzed by the supplier
for composition and contaminant levels. The diet formula is presented in appendix 2. Drinking water filtered by a FG Millipore membrane (0.22
micron) was provided ad libitum. Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses
include the detection of possible contaminants (pesticides, heavy metals and nitrosamines). No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A limit test was performed by application of 2000 mg/kg of the test item to one group of ten animals (five males and five females).

On the day before treatment, the dorsal area of each animal was clipped (i.e. approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females) using an electric clipper. Only animals with healthy intact skin were used for the study. A single dose of 2000 mg/kg of the test item in its original form was placed on a hydrophilic gauze pad (pre-moistened with 2 mL of purified water) and then applied to an area of the skin representing approximately 10% of the total body surface of the animals, calculated according to Meeh's formula (i.e. approximately 5 cm x 7 cm for the males and 5 cm x 6 cm
for the females). The test item and the gauze pad were held in contact with the skin for 24 hours by means of an
adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. This dressing prevented ingestion of the test item by the
animal. On removal of the dressing, any residual test item was removed using a dry cotton pad. The dose applied to each animal was adjusted
according to the body weight determined on the day of treatment.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical
signs. Thereafter, observation of the animals was made at least once a day until day 15. Type, time of onset and duration of clinical signs were
recorded for each animal individually. From day 2, any local cutaneous reaction was recorded.

The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.

On day 15, all animals were killed by carbon dioxide asphyxiation. All study animals were subjected to a macroscopic examination as soon as
possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart,
kidneys,liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. No organ samples were taken.
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
None
Body weight:
A slightly reduced weight gain was obsrved in 2/5 females during the second week of the study.
Gross pathology:
No apparent abnormalities
Other findings:
No cutaneous reactions were observed

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of dilauroyl peroxide to rats was greater than 2000 mg/kg.
Executive summary:

The study was conducted to determine the acute dermal toxicity of dilauroyl peroxide to rats following the 24 hour application of 2000 mg/kg bodyweight. Test animals were observed for 14 days following application.

There were no mortalities or clinical signs of toxicity. There were no cutaneous reactions.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Two acute oral gavage studies in rats are available which demonstrate the lack of toxicity of dilauroyl peroxide by this route. The more recent apparently well conducted GLP study conducted at 2000 mg/kg did not elicit mortalities when administered to rats by gavage (Rees, 1993). In an older non-GLP study with limited documentation, there were no mortalities when rats were administered 5000 mg/kg by gavage (Wazeter, 1973). These studies demonstrate a low potential for acute oral hazard.

In an apparently well conducted GLP acute dermal study, dilauroyl peroxide applied to rabbits at 2000 mg/kg did not elicit mortalities (Ollivier, 2004). Dilauroyl peroxide does not appear to pose an acute dermal hazard.

Although documentation is limited in an available acute inhalation study, a test atmosphere containing 200 mg/l of dilauroyl peroxide dust induced 6/10 mortalities. The LC50 is predicted to be well above the limit dose of 5 mg/l. In addition granulometry data demonstrates there are no significant particles less than 100 microns. Therefore the inhalation hazard of dilauroyl peroxide is considered low.

Justification for classification or non-classification

Acute toxicity studies demonstrate that dilauroyl peroxide does not meet the criteria for classification.

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